Results of the Two Incidence Screenings in the National Lung Screening Trial

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).

MA 14.07 Randomized Lung Cancer Screening with Low-Dose CT in China: A Specific Risk-Based Screening for Chinese Population

BackgroundLung cancer is the largest contributor to mortality from cancer. The National Lung Screening Trial (NLST) showed that screening with low-dose helical computed tomography (CT) rather than with chest radiography reduced mortality from lung cancer. We describe the screening, diagnosis, and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer–screening programs.MethodsAt 33 U.S. centers, from August 2002 through April 2004, we enrolled asymptomatic participants, 55 to 74 years of age, with a history of at least 30 pack-years of smoking. The participants were randomly assigned to undergo annual screening, with the use of either low-dose CT or chest radiography, for 3 years. Nodules or other suspicious findings were classified as positive results. This article reports findings from the initial screening examination.ResultsA total of 53,439 eligible participants were randomly assigned to a study group (26,715 to low-dose CT and 26,724 to chest radiography); 26,309 participants (98.5%) and 26,035 (97.4%), respectively, underwent screening. A total of 7191 participants (27.3%) in the low-dose CT group and 2387 (9.2%) in the radiography group had a positive screening result; in the respective groups, 6369 participants (90.4%) and 2176 (92.7%) had at least one follow-up diagnostic procedure, including imaging in 5717 (81.1%) and 2010 (85.6%) and surgery in 297 (4.2%) and 121 (5.2%). Lung cancer was diagnosed in 292 participants (1.1%) in the low-dose CT group versus 190 (0.7%) in the radiography group (stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112). Sensitivity and specificity were 93.8% and 73.4% for low-dose CT and 73.5% and 91.3% for chest radiography, respectively.ConclusionsThe NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography, suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.)

Overcoming perceived hurdles in lung cancer screening: the low risk of complications of image-guided transthoracic needle biopsy.

When Will Enough Ever Be Enough?

Lung cancer screening (LCS) using low-dose computed tomography (LDCT) reduces lung cancer mortality but can lead to downstream procedures, complications, and other potential harms. Estimates of these events outside NLST (National Lung Screening Trial) have been variable and lacked evaluation by screening result, which allows more direct comparison with trials. To identify rates of downstream procedures and complications associated with LCS. Retrospective cohort study. 5 U.S. health care systems. Individuals who completed a baseline LDCT scan for LCS between 2014 and 2018. Outcomes included downstream imaging, invasive diagnostic procedures, and procedural complications. For each, absolute rates were calculated overall and stratified by screening result and by lung cancer detection, and positive and negative predictive values were calculated. Among the 9266 screened patients, 1472 (15.9%) had a baseline LDCT scan showing abnormalities, of whom 140 (9.5%) were diagnosed with lung cancer within 12 months (positive predictive value, 9.5% [95% CI, 8.0% to 11.0%]; negative predictive value, 99.8% [CI, 99.7% to 99.9%]; sensitivity, 92.7% [CI, 88.6% to 96.9%]; specificity, 84.4% [CI, 83.7% to 85.2%]). Absolute rates of downstream imaging and invasive procedures in screened patients were 31.9% and 2.8%, respectively. In patients undergoing invasive procedures after abnormal findings, complication rates were substantially higher than those in NLST (30.6% vs. 17.7% for any complication; 20.6% vs. 9.4% for major complications). Assessment of outcomes was retrospective and was based on procedural coding. The results indicate substantially higher rates of downstream procedures and complications associated with LCS in practice than observed in NLST. Diagnostic management likely needs to be assessed and improved to ensure that screening benefits outweigh potential harms. National Cancer Institute and Gordon and Betty Moore Foundation.

Low-dose computed tomography (LDCT) has shown promise in the early detection of lung cancer in prior observational studies. The National Lung Screening Trial (NLST) is the largest multicenter, randomized, controlled trial comparing LDCT with chest radiography with an intention-to-screen analysis (1). High-risk (.30 pack-years) active or ex-smokers between 55 and 74 years of age (n 1⁄4 53,454) were screened three times at 1-year intervals and followed for a median of 6.5 years. Lesions suspicious for cancer (noncalcified nodules . 4 mm) were found in 39.1% of individuals with LDCT and 16.0% with radiography during the trial. A total of 96.4% of these lesions in the LDCT group and 94.5% in the radiography group were false-positive results. The LDCT group had 247 deaths from lung cancer per 100,000 person-years and the radiography group had 309 deaths per 100,000 person-years. This meant a 20% (95% CI, 6.8–26.7; P 1⁄4 0.004) relative reduction in mortality from lung cancer, and a 6.7% (95% CI, 1.2–13.6; P 1⁄4 0.02) reduction in all-cause mortality with LDCT screening. Of the 17,053 LDCT lesions suspicious for cancer in which cancer was not confirmed, 457 (2.7%) resulted in an invasive procedure, with 11 (0.06%) major complications. Multiple unanswered questions regarding lung cancer screening remain. First, this study was done at large centers of excellence, with potentially different results at smaller hospitals. Second, 1,060 individuals in the LDCT and 941 in the radiography group were found to have lung cancer, suggesting the possibility of overdiagnosis with LDCT (2). Are there individuals who die with, rather than from, lung cancer (3)? Third, the implications for smoking cessation are unclear. Smokers might use screening as a tool to continue smoking. Alternatively, a positive screening test might also induce smokers to quit. Last, there are unanswered questions about the optimal demographic group to screen (age, sex, and smoking history), frequency and duration of screening, risks of increasing radiation exposure, risks of false-positive tests, and cost. The number of LDCT screening tests needed to prevent one lung cancer death was 320. I believe this study should not inform health policy decision making until these questions are better answered.

Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial

Two large randomised controlled trials of screening for lung cancer with low-dose CT (LDCT)—the National Lung Screening Trial (NLST) and the Dutch-Belgian lung cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek...

Lung cancer screening with low-dose computed tomography (LDCT) has been recommended, based primarily on the results of the NLST (National Lung Screening Trial). The American College of Radiology recently released Lung-RADS, a classification system for LDCT lung cancer screening. To retrospectively apply the Lung-RADS criteria to the NLST. Secondary analysis of a group from a randomized trial. 33 U.S. screening centers. Participants were randomly assigned to the LDCT group of the NLST, were aged 55 to 74 years, had at least a 30-pack-year history of smoking, and were current smokers or had quit within the past 15 years. 3 annual LDCT lung cancer screenings. Lung-RADS classifications for LDCT screenings. Lung-RADS categories 1 to 2 constitute negative screening results, and categories 3 to 4 constitute positive results. Of 26 722 LDCT group participants, 26 455 received a baseline screening; 48 671 screenings were done after baseline. At baseline, the false-positive result rate (1 minus the specificity rate) for Lung-RADS was 12.8% (95% CI, 12.4% to 13.2%) versus 26.6% (CI, 26.1% to 27.1%) for the NLST; after baseline, the false-positive result rate was 5.3% (CI, 5.1% to 5.5%) for Lung-RADS versus 21.8% (CI, 21.4% to 22.2%) for the NLST. Baseline sensitivity was 84.9% (CI, 80.8% to 89.0%) for Lung-RADS versus 93.5% (CI, 90.7% to 96.3%) for the NLST, and sensitivity after baseline was 78.6% (CI, 74.6% to 82.6%) for Lung-RADS versus 93.8% (CI, 91.4% to 96.1%) for the NLST. Lung-RADS criteria were applied retrospectively. Lung-RADS may substantially reduce the false-positive result rate; however, sensitivity is also decreased. The effect of using Lung-RADS criteria in clinical practice must be carefully studied. National Institutes of Health.

In head and neck cancer survivors, lung cancer screening may aid in detecting a second primary lung cancer or metastatic head and neck cancer earlier in the course of disease, which may improve treatment outcomes. However, no randomized data exist to assess the value of lung cancer screening in this population. To evaluate the incidence of second primary lung cancer in survivors of head and neck cancer survivors with screening low-dose computed tomography (CT) vs chest radiography (CXR). For this ad hoc secondary analysis of a randomized clinical trial, head and neck cancer survivors were identified from the National Lung Screening Trial, which enrolled participants from August 2002 to April 2004. This randomized clinical trial compared screening using low-dose CT chest vs CXR in patients aged 55 to 74 years with at least a 30 pack-year history of cigarette smoking and who were current smokers or had quit within the past 15 years and who were at high risk for lung cancer. The incidences of second primary lung cancer and second primary head and neck cancer were compared with screening using low-dose CT vs CXR. Data were analyzed from December 1, 2020, to June 30, 2021. Screening low-dose CT of the chest vs CXR. The primary outcome was the incidence of a second primary lung cancer. Among 53 452 enrolled participants, we identified 171 survivors of head and neck cancer, of whom 82 were screened with low-dose CT of the chest and 89 with CXR. Participants' mean (SD) age was 61 (5) years, and 132 were men (77.2%). The incidence of lung cancer was higher among head and neck cancer survivors compared with participants without head and neck cancer (2080 per 100 000 person-years [2.1%] vs 609 per 100 000 person-years [0.6%]; adjusted rate ratio, 2.54; 95% CI, 1.63-3.95). In head and neck cancer survivors, the incidence of second primary lung cancer was 2610 cases per 100 000 person-years in the low-dose CT group vs 1594 cases per 100 000 person-years in the CXR group (rate ratio, 1.55; 95% CI, 0.59-3.63). In head and neck cancer survivors, overall survival was 7.07 years with low-dose CT vs 6.66 years with CXR (log-rank P = .48). The results of this ad hoc secondary analysis of a randomized clinical trial suggest that head and neck cancer survivors are at especially high risk for a second primary lung cancer. These findings underscore the importance of low-dose CT screening in head and neck cancer survivors with significant cigarette smoking history who are fit to undergo treatment with curative intent.

58 Background: Lung cancer screening (LCS) with Low dose computed-tomography (LDCT) has been recommended by USPSTF for high-risk population since 2013 largely based on 20% relative reduction in lung cancer mortality shown in National Lung Screening Trial (NLST). The success of NLST was related to its high adherence rate and thorough ascertainment of lung cancers and deaths. This study evaluated performance of lung cancer screening program in Histoplasmosis endemic community. Methods: Demographic and clinical information was collected through retrospective review on all patients in the lung cancer screening program of a Kentucky health system comprising 21 centers from 2016 and 2017. A positive LDCT screen is defined as Lung-RADS version 1.0 assessment categories 3 or 4. Results: A total of 4500 LDCT screens were performed in 2016 (39%) and 2017 (61%) with 49% adherence rate to repeat annual screen in 2017. Mean age of patients was 64 years, majority being females (54%) and current smokers (69%) with average 52-pack year smoking history. The rate of positive LDCT was 13.3% (600) varying based on initial (14.6%) vs annual (9.5%) screen. A total of 70 lung cancers were diagnosed among all positive LDCT screens (11.7%) with a false positive rate of 12%. Conclusions: Comparing to NLST results updated with Lung-RADS categories, baseline positive screens in our community are similar (14.6% vs 13.6%, p = 0.15) despite being a Histoplasmosis endemic region. Our higher rate of annual positive screens (9.5% vs 6%, p < 0.001) and false positive rate (12% vs 8%, p < 0.001) may be explained by poor adherence to annual screens and an inability to thoroughly ascertain lung cancer diagnosis in all patients due to lost to follow up. In community setting with < 50% adherence to annual screens compared to 95% adherence in NLST, it is unclear if LCS mortality benefit still holds and needs intervention to increase adherence to LCS.

Evaluation of: National Lung Screening Trial Research Team, Church TR, Black WC, Aberle DR et al. Results of initial low-dose computed tomographic screening for lung cancer. N. Engl. J. Med. 368, 1980-1991 (2013). In 2011, the US NLST trial demonstrated that mortality from lung cancer can be reduced by using low-dose computed tomography (LDCT) screening rather than chest x-ray (CXR) screening. This paper from the US NLST research team focuses on the results of the initial round of LDCT for lung cancer. A total of 53,439 participants were included and randomly assigned to LDCT screening (n = 26,715) or CXR screening (n = 26,724). In total, 27.3% of the participants in the LDCT group and 9.2% in the CXR group had a positive screening result. As a result, 3.8% (LDCT group) and 5.7% (CXR group) of these subjects were diagnosed with lung cancer. The sensitivity (93.8%) and specificity (73.4%) for lung cancer were higher for LDCT compared with CXR screening; 73.5 and 91.3%, respectively.

Recommendations vary regarding the maximum age at which to stop lung cancer screening: 80 years according to the U.S. Preventive Services Task Force (USPSTF), 77 years according to the Centers for Medicare & Medicaid Services (CMS), and 74 years according to the National Lung Screening Trial (NLST). To compare the cost-effectiveness of different stopping ages for lung cancer screening. By using shared inputs for smoking behavior, costs, and quality of life, 4 independently developed microsimulation models evaluated the health and cost outcomes of annual lung cancer screening with low-dose computed tomography (LDCT). The NLST; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; SEER (Surveillance, Epidemiology, and End Results) program; Nurses' Health Study and Health Professionals Follow-up Study; and U.S. Smoking History Generator. Current, former, and never-smokers aged 45 years from the 1960 U.S. birth cohort. 45 years. Health care sector. Annual LDCT according to NLST, CMS, and USPSTF criteria. Incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100000 per quality-adjusted life-year (QALY). The 4 models showed that the NLST, CMS, and USPSTF screening strategies were cost-effective, with ICERs averaging $49200, $68600, and $96700 per QALY, respectively. Increasing the age at which to stop screening resulted in a greater reduction in mortality but also led to higher costs and overdiagnosis rates. Probabilistic sensitivity analysis showed that the NLST and CMS strategies had higher probabilities of being cost-effective (98% and 77%, respectively) than the USPSTF strategy (52%). Scenarios assumed 100% screening adherence, and models extrapolated beyond clinical trial data. All 3 sets of lung cancer screening criteria represent cost-effective programs. Despite underlying uncertainty, the NLST and CMS screening strategies have high probabilities of being cost-effective. CISNET (Cancer Intervention and Surveillance Modeling Network) Lung Group, National Cancer Institute.

The improvement of pulmonary nodule detection, which is a challenging task when using chest radiographs, may help to elevate the role of chest radiographs for the diagnosis of lung cancer. To assess the performance of a deep learning-based nodule detection algorithm for the detection of lung cancer on chest radiographs from participants in the National Lung Screening Trial (NLST). This diagnostic study used data from participants in the NLST ro assess the performance of a deep learning-based artificial intelligence (AI) algorithm for the detection of pulmonary nodules and lung cancer on chest radiographs using separate training (in-house) and validation (NLST) data sets. Baseline (T0) posteroanterior chest radiographs from 5485 participants (full T0 data set) were used to assess lung cancer detection performance, and a subset of 577 of these images (nodule data set) were used to assess nodule detection performance. Participants aged 55 to 74 years who currently or formerly (ie, quit within the past 15 years) smoked cigarettes for 30 pack-years or more were enrolled in the NLST at 23 US centers between August 2002 and April 2004. Information on lung cancer diagnoses was collected through December 31, 2009. Analyses were performed between August 20, 2019, and February 14, 2020. Abnormality scores produced by the AI algorithm. The performance of an AI algorithm for the detection of lung nodules and lung cancer on radiographs, with lung cancer incidence and mortality as primary end points. A total of 5485 participants (mean [SD] age, 61.7 [5.0] years; 3030 men [55.2%]) were included, with a median follow-up duration of 6.5 years (interquartile range, 6.1-6.9 years). For the nodule data set, the sensitivity and specificity of the AI algorithm for the detection of pulmonary nodules were 86.2% (95% CI, 77.8%-94.6%) and 85.0% (95% CI, 81.9%-88.1%), respectively. For the detection of all cancers, the sensitivity was 75.0% (95% CI, 62.8%-87.2%), the specificity was 83.3% (95% CI, 82.3%-84.3%), the positive predictive value was 3.8% (95% CI, 2.6%-5.0%), and the negative predictive value was 99.8% (95% CI, 99.6%-99.9%). For the detection of malignant pulmonary nodules in all images of the full T0 data set, the sensitivity was 94.1% (95% CI, 86.2%-100.0%), the specificity was 83.3% (95% CI, 82.3%-84.3%), the positive predictive value was 3.4% (95% CI, 2.2%-4.5%), and the negative predictive value was 100.0% (95% CI, 99.9%-100.0%). In digital radiographs of the nodule data set, the AI algorithm had higher sensitivity (96.0% [95% CI, 88.3%-100.0%] vs 88.0% [95% CI, 75.3%-100.0%]; P = .32) and higher specificity (93.2% [95% CI, 89.9%-96.5%] vs 82.8% [95% CI, 77.8%-87.8%]; P = .001) for nodule detection compared with the NLST radiologists. For malignant pulmonary nodule detection on digital radiographs of the full T0 data set, the sensitivity of the AI algorithm was higher (100.0% [95% CI, 100.0%-100.0%] vs 94.1% [95% CI, 82.9%-100.0%]; P = .32) compared with the NLST radiologists, and the specificity (90.9% [95% CI, 89.6%-92.1%] vs 91.0% [95% CI, 89.7%-92.2%]; P = .91), positive predictive value (8.2% [95% CI, 4.4%-11.9%] vs 7.8% [95% CI, 4.1%-11.5%]; P = .65), and negative predictive value (100.0% [95% CI, 100.0%-100.0%] vs 99.9% [95% CI, 99.8%-100.0%]; P = .32) were similar to those of NLST radiologists. In this study, the AI algorithm performed better than NLST radiologists for the detection of pulmonary nodules on digital radiographs. When used as a second reader, the AI algorithm may help to detect lung cancer.